Patients with cancer often have a reduced capacity to mount cellular or humoral immune responses. An extreme example of this is provided by patients with multiple myeloma and by mice with plasmacytomas (the murine model of human myeloma). Because localized subcutaneous plasmacytomas (PC) depress the antibody response of lymphoid tissue not infiltrated by the tumor, because immunocompetence seems to return when the tumor has been eliminated, because it has been shown that the immune response can be regulated by humoral substances produced by cells of the lymphoid series, and because several other explanations of PC-induced immunosuppression have been ruled out by our previous work, we propose, that the immune impairment observed in mice bearing PC may be caused by a regulatory substance produced by the tumor itself or by non-malignant cells activated by the tumor. Preliminary studies support this hypothesis. Our experiments are therefore designed to extend these findings, to determine what cell is making this substance, to demonstrate its presence in the culture supernatant of the identified cell and eventually to isolate and characterize this factor. In order to attain these objectives, an assay for this substance must be developed. We propose to test the supernatants of cultured myeloma cells or tumor-activated lymphocytes for this regulatory substance. This will be done using standard techniques of immunobiology: the Mishell-Dutton technique of antibody induction in vitro; mixed lymphocyte culture, adoptive immune reconstitution of irradiated animals, mitogenic stimulation of T and B cells. We will also examine whether this substance is produced or induced only by plasmacytomas, by malignant B cells, by all malignant lymphoid tissue, or by malignant cells in general.